The development of cancer is generally thought of as the result of many acquired genetic changes that ultimately produce a malignant phenotype. Age-related onset and a history of sun exposure are typical for acquired cases of non-melanoma skin cancer (NMSC) which is the most common malignancy of older individuals and represents one of the most common needs for surgical procedures in this population. Inherited or acquired mitochondrial disorders often have an age-related onset. Mitochondria are organelles responsible for generating much of the necessary energy and these organelles contain their own DNA genome. Mitochondria have recently become a focal point for apoptosis research and now tumor biology. The purpose of this study is to test the hypothesis that mitochondrial DNA (mtDNA) is a target of photoaging and that mtDNA mutations play a role in the development of NMSC. This proposal seeks specifically to fully characterize the mitochondrial genome of photo- aged human skin, of benign squamous neoplasms, and of NMSC tumor specimens and correlate these findings with observed biological behavior of these lesions. In addition, the functional effects of these mtDNA mutations will be studied in cell hybrid systems for their effect on the growth of non-malignant cells. The insights gained from this research may be useful in our ability to target specific biological behavior of tumor cells with medications as an alternative to surgery for patients with these very common malignancies.